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https://www.readbyqxmd.com/read/27920093/metformin-reduces-glycometabolism-of-papillary-thyroid-carcinoma-in-vitro-and-in-vivo
#1
Chen-Tian Shen, Wei-Jun Wei, Zhong-Ling Qiu, Hong-Jun Song, Xin-Yun Zhang, Zhen-Kui Sun, Quan-Yong Luo
More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by (18)F-FDG uptake assay and western blotting analysis, respectively...
January 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#2
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27916907/metformin-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-via-pkm2-relative-mtor-p70s6k-signaling-pathway-in-cervical-carcinoma-cells
#3
Keyan Cheng, Min Hao
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. METHODS: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#4
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27856330/metformin-suppresses-adipogenesis-through-both-amp-activated-protein-kinase-ampk-dependent-and-ampk-independent-mechanisms
#5
Suet Ching Chen, Rebecca Brooks, Jessica Houskeeper, Shaun K Bremner, Julia Dunlop, Benoit Viollet, Pamela J Logan, Ian P Salt, S Faisal Ahmed, Stephen J Yarwood
People with Type 2 diabetes mellitus (T2DM) have reduced bone mineral density and an increased risk of fractures due to altered mesenchymal stem cell (MSC) differentiation in the bone marrow. This leads to a shift in the balance of differentiation away from bone formation (osteogenesis) in favour of fat cell development (adipogenesis). The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health...
November 14, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27856287/the-inhibition-of-spinal-synaptic-plasticity-mediated-by-activation-of-amp-activated-protein-kinase-signaling-alleviates-the-acute-pain-induced-by-oxaliplatin
#6
Yun-Zhi Ling, Zhen-Yu Li, Han-Dong Ou-Yang, Chao Ma, Shao-Ling Wu, Jia-You Wei, Huan-Huan Ding, Xiao-Long Zhang, Meng Liu, Cui-Cui Liu, Zhen-Zhen Huang, Wen-Jun Xin
Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg)...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27814614/metformin-suppresses-crc-growth-by-inducing-apoptosis-via-adora1
#7
Bin Lan, Jian Zhang, Peng Zhang, Weihong Zhang, Shugang Yang, Dong Lu, Wenqin Li, Qinbao Dai
Accumulating evidence suggests that the anti-diabetic drug, metformin, exerts anti-proliferative effects in many types of cancers. However, the function and mechanisms of metformin in human colorectal cancer (CRC) remain unknown. Here, we show that metformin induces growth inhibition and apoptosis through activating AMPK-mTOR pathway in human colorectal cancer cells. Notably, metformin treatment significantly up-regulated adenosine A1 receptor (ADORA1) expression in human colorectal cancer cells, while suppression of ADORA1 activity by its specific inhibitor rescued the growth inhibition induced by metformin...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27812983/ampk-as-a-pro-longevity-target
#8
Kristopher Burkewitz, Heather J M Weir, William B Mair
Chronic, age-associated diseases are already among the leading causes of morbidity and death in the world, a problem exacerbated by the rapidly rising proportion of elderly in the global population. This emergent epidemic represents the next great challenge for biomedical science and public health. Fortunately, decades of studies into the biology of aging have provided a head start by revealing an evolutionarily conserved network of genes that controls the rate and quality of the aging process itself and which can thereby be targeted for protection against age-onset disease...
2016: EXS
https://www.readbyqxmd.com/read/27803295/strong-antineoplastic-effects-of-metformin-in-preclinical-models-of-liver-carcinogenesis
#9
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard van Beers, Sandrine Faivre, Pierre Bedossa, Valerie Paradis
Studies suggest that metformin, widely used for treating type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma, metformin may provide antitumoral effects  We evaluated the impact of metformin on tumor growth and visceral fat composition using relevant preclinical models of metabolic syndrome.  EXPERIMENTAL DESIGN: Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow-diet (SC), 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured hepatocellular carcinoma slices...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27802188/metformin-enhances-the-radiosensitivity-of-human-liver-cancer-cells-to-%C3%AE-rays-and-carbon-ion-beams
#10
Eun Ho Kim, Mi-Sook Kim, Yoshiya Furusawa, Akiko Uzawa, Soorim Han, Won-Gyun Jung, Sei Sai
The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27796611/synergy-of-2-deoxy-d-glucose-combined-with-berberine-in-inducing-the-lysosome-autophagy-and-transglutaminase-activation-facilitated-apoptosis
#11
H Dorota Halicka, Jorge Garcia, Jiangwei Li, Hong Zhao, Zbigniew Darzynkiewicz
Utilizing a variety of flow cytometric methods evidence was obtained indicating that a combination of the glucose analog 2-deoxy-D-glucose (2-dG) and the plant alkaloid berberine (BRB) produces synergistic effect in the induction of apoptosis in human lymphoblastoid TK6 cells. The synergistic effect is seen at concentrations of the drugs at which each of them alone shows no cytotoxicity at all. The data suggest that the combination of these drugs, which are known in terms of their overall toxicity, side effects and pharmacokinetics may be considered for further studies as chemopreventive and cancer treatment modalities...
October 28, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27753529/cyclin-g2-promotes-cell-cycle-arrest-in-breast-cancer-cells-responding-to-fulvestrant-and-metformin-and-correlates-with-patient-survival
#12
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27748082/metformin-induces-degradation-of-mtor-protein-in-breast-cancer-cells
#13
Mohamed Alalem, Alpana Ray, Bimal K Ray
Activation of mTOR is implicated in the development and progression of breast cancer. mTOR inhibition exhibited promising antitumor effects in breast cancer; however, its effect is compromised by several feedback mechanisms. One of such mechanisms is the upregulation of mTOR pathway in breast cancer cells. Despite the established role of mTOR activation in breast cancer, the status of total mTOR protein and its impact on the tumor behavior and response to treatment are poorly understood. Besides, the mechanisms underlying mTOR protein degradation in normal and cancer breast cells are still largely unknown...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27745917/prospective-evaluation-of-the-molecular-effects-of-metformin-on-the-endometrium-in-women-with-newly-diagnosed-endometrial-cancer-a-window-of-opportunity-study
#14
Pamela T Soliman, Qian Zhang, Russell R Broaddus, Shannon N Westin, David Iglesias, Mark F Munsell, Rosemarie Schmandt, Melinda Yates, Lois Ramondetta, Karen H Lu
OBJECTIVE: Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. METHODS: In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery...
December 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27698900/anti-inflammatory-and-antitumor-activity-of-a-triple-therapy-for-a-colitis-related-colorectal-cancer
#15
Gabriela Figueroa-González, Verónica García-Castillo, Jossimar Coronel-Hernández, Eduardo López-Urrutia, Sonia León-Cabrera, Luis E Arias-Romero, L I Terrazas, Miriam Rodríguez-Sosa, Alma Delia Campos-Parra, Eduardo Zúñiga-Calzada, Cesar Lopez-Camarillo, Fermín Morales-González, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Colorectal cancer (CRC) is an important health issue worldwide, accounting for the third place of cancer incidence. Chronic inflammation, as seen in Crohn's disease and ulcerative colitis, is the most important risk factor for developing CRC, as it favours neoplastic transformation by enhancing epithelial cell turnover in the colonic mucosa. Treatments for CRC need to be improved; currently they are not specific and have several secondary effects in patients. The main objective of this work was to evaluate a new therapeutic strategy against a colitis-related colorectal cancer in vivo and in vitro by targeting mTOR-signaling and lactate dehydrogenase A...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27627216/nephroprotective-effects-of-metformin-in-diabetic-nephropathy
#16
Sreenithya Ravindran, Vinitha Kuruvilla, Kerry Wilbur, Shankar Munusamy
Metformin, a well-known anti-diabetic agent, is very effective in lowering blood glucose in patients with type 2 diabetes with minimal side-effects. Metformin is also being recommended in the treatment of obesity and polycystic ovary syndrome. Metformin elicits its therapeutic effects mainly via activation of AMP-activated kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and activation of pathologic pathways such as mammalian target of rapamycin (mTOR), endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), oxidative stress, and hypoxia...
September 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27600020/activation-of-ampk-%C3%AE-2-inhibits-airway-smooth-muscle-cells-proliferation
#17
Lu Liu, Yilin Pan, Yang Song, Xiaofan Su, Rui Ke, Lan Yang, Li Gao, Manxiang Li
The aims of the present study were to examine the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on airway smooth muscle cells (ASMCs) proliferation and to address its potential mechanisms. Platelet derived growth factor (PDGF) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, and this in turn up-regulated S-phase kinase-associated protein 2 (Skp2) and consequently reduced cyclin dependent kinase inhibitor 1B (p27) leading to ASMCs proliferation...
September 4, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27585117/protective-effect-of-metformin-in-an-aberrant-crypt-foci-model-induced-by-1-2-dimethylhydrazine-modulation-of-oxidative-stress-and-inflammatory-process
#18
Heloíza Paranzini Bordini, Jean Lucas Kremer, Tatiane Renata Fagundes, Gabriella Pasqual Melo, Ivete Conchon Costa, Suelen Santos Da Silva, Alessandra Lourenço Cecchini, Carolina Panis, Rodrigo Cabral Luiz
Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET - an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis...
September 1, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27577068/sirolimus-and-metformin-synergistically-inhibit-hepatocellular-carcinoma-cell-proliferation-and-improve-long-term-survival-in-patients-with-hcc-related-to-hepatitis-b-virus-induced-cirrhosis-after-liver-transplantation
#19
Chuan Shen, Chenghong Peng, Baiyong Shen, Zhecheng Zhu, Ning Xu, Tao Li, Junjie Xie
Immunosuppressive agents used postoperatively after liver transplantation (LT) for hepatocellular carcinoma (HCC) favor recurrence and metastasis. Therefore, new effective immunosuppressants are needed. This retrospective study assessed combined sirolimus and metformin on survival of HCC patients after LT. In 2001-2013, 133 HCC patients with LT were divided into four groups: sirolimus and metformin combination (Sir+Met), sirolimus monotherapy (Sir), other immunosuppressants in diabetes mellitus (DM) patients without metformin (No Sir with DM), and other immunosuppressants in patients without DM (No Sir without DM)...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27576133/metformin-inhibits-jak2v617f-activity-in-mpn-cells-by-activating-ampk-and-pp2a-complexes-containing-the-b56%C3%AE-subunit
#20
Ichiro Kawashima, Keita Kirito
Metformin suppresses the growth of a variety of malignant hematologic cells. It is widely accepted that metformin inhibits the growth of malignant cells primarily by suppressing the mTOR pathway or regulating autophagy. In contrast, we found another possible mechanism that inhibits the growth of malignant cells, suppression of the activity of the oncogenic kinase JAK2V617F. We identified at least two distinct mechanisms involved in metformin-induced JAK2V617F inhibition. First, metformin increases reactive oxygen species levels in these cells, leading to the inhibition of SHP-2, a positive regulator of JAK2V617F...
August 27, 2016: Experimental Hematology
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